Novel pH-responsive and CD44-targeting silica nanoparticles for inflammatory bowel disease therapy

• The nanoparticles target the inflamed areas in the intestines and can sustainably release anti-inflammatory salviolic acid. • The nanoparticles clear ROS and protect mitochondria from damage caused by ROS. • The nanoparticles repair damaged intestinal barrier and reduce inflammation levels. • Nanoparticles improve the disorder of the gut microbiome. The prevalence of inflammatory bowel disease (IBD) is on the rise, with current therapeutic options offering limited efficacy, which significantly affects patients’ quality of life. IBD is a multifaceted disorder characterized by dysfunction of mucosal immune system dysfunction, genetic mutations, and environmental influences. To address these challenges, we developed chondroitin sulfate (CS)-modified mesoporous silica nanoparticles (MSNs) loaded with carnosic acid (CA), following coated with an enteric material to get the controlled-release formulations (CA@MS-E) with the characters of pH stability and dual targeting. Oral administration of CA@MS-E effectively protects the drug from degradation by gastric acid and ensures targeted delivery to the colon, where it scavenges overexpressed reactive oxygen species (ROS) and exerts therapeutic effects. In a mouse model of acute colitis, the therapeutic effect of CA@MS-E was markedly superior to that of the clinical control drug sulfasalazine with the properties in mitochondrial protection, apoptosis reduction, and intestinal flora regulatio. In conclusion, oral nanomedicine presents a promising strategy to enhance the therapeutic potential of small molecule drugs for IBD treatment.